Neuroactive substituted cyclopenta[b]phenanthrenes as modulators for GABA type-A receptors

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof;
• wherein:
• R1 is H, ═O, ═CHCN, ═CHCO2Rz, where Rz is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-CN, β-OH, β-ORy, where Ry is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-NO2, spiroepoxy, or C(O)Rx, where Rx is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R2 is H, ═O, ═CHCN, ═CHCO2Rw, where Rw is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-CN, β-OH, β-ORv, where Rv is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-NO2, spiroepoxy, or C(O)Ru, where Ru is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R3 is H, ═O, ═CHCN, ═CHCO2Rt, where Rt is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, —CN, β-OH, β-ORs, where Rs is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-NO2, spiroepoxy, or C(O)Rr, where Rr is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R4 is H, optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R5 is H, CO2Rq, where Rq is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, CH2ORp, where Rp is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, C(O)Ro, where Ro is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, C(O)NHRn, where Rn is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, CH2NHRm, where Rm is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, CH2N(CH3)2, or CH2N(CH2CH3)2;
• R6 is H, ═O, N(CH3)2, N(CH2CH3)2, ORl, where Rl is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, or NRk, where Rk is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl;
• R7 is H, ═O, N(CH3)2, N(CH2CH3)2, ORj, where Rj is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, or NRi, where Ri is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl;
• R8 is H, N(CH3)2, N(CH2CH3)2, optionally substituted morpholinyl, or ORh, where Rh is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl;
• R9 is H, optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl;
• R10 is H, optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R11 is H or C(O)Rg, where Rg is optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl, or optionally substituted C2-C20 alkynyl;
• - - - - - denotes an optional, additional C—C bond, resulting in either a C═C bond between, C1-C2, C4-C4a, C4a-C5, C8-C9, or C9-C10, with the provisos that when present between:
• (i) C4-C4a, the C4a—H substituent is not present;
• (ii) C4a-C5, the C4a—H substituent is not present and R7 is other than ═O;
• (iii) C9-C10, R1 is other than ═O, ═CHCN or ═CHCO2Rz, and R2 is other than ═O, ═CHCN or ═CHCO2Rw;
• and, (iv) C8-C9, R2 is other than ═O, ═CHCN or ═CHCO2Rw, and R3 is other than ═O, ═CHCN or ═CHCO2Rt;
• and,
• with the proviso that:
• when C4a—H is in the α-configuration, R4=methyl and R1=R2=R5=R6=R7=R8=R9=R10=R11 is H, R3 is other than ═O or spiroepoxy.